Blast Injured Soldiers' Brains Mimic Athletes'

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In a case series of postmortem brain studies from U.S. military veterans exposed to blast and/or concussive injury, the investigators found evidence of chronic traumatic encephalopathy (CTE), a tau protein–linked neuro-degenerative disease, similar to the CTE neuropathology observed in young American football players.

Note that the investigators were able to develop a blast neurotrauma mouse model that recapitulated CTE-linked neuropathology and may help to provide evidence of mechanisms for the damage.

Autopsies on the brains of military veterans who experienced traumatic brain injury from a blast showed pathologic similarities to the brains of athletes who'd had repetitive concussions that led to chronic traumatic encephalopathy (CTE), researchers found.

Neuropathologic examinations of the brains of four veterans identified neurofibrillary and glial tangles containing the abnormal protein tau throughout various regions, including the frontal and parietal cortex and hippocampus, according to Lee E. Goldstein, MD, PhD, of Boston University, and colleagues.

There also was clear evidence of degeneration of axons in white matter adjoining the areas of tau deposition.

The brains of four athletes showed similar tau-based tangles and axonal loss, findings that were not present in the brains of four young adults who died from unrelated causes and with no history of brain injury, the researchers reported online in Science Translational Medicine.

These injuries were "indistinguishable" from those seen in athletes like Dave Duerson, who died of a self-inflicted gunshot wound after years of psychiatric deterioration following a football career characterized by multiple head injuries.

To explore the potential mechanisms of these changes, the researchers developed a mouse model of neurotrauma simulating the conditions of a blast from an improvised explosive device, such as those widely detonated throughout Iraq and Afghanistan.

In this model, they were able to measure the strength of the blast wave, which had a Mach number of 1.26, followed by wind velocities exceeding 330 miles per hour, which is much higher than any naturally occurring gust of wind.

This blast wind led to oscillating acceleration-deceleration effects on the murine head, with radial acceleration reaching 954 krad/s2.

The acceleration-deceleration injuries, in turn, led to neuropathologic changes similar to those in the human cases, with phosphorylated tau, axonal dystrophy, and degeneration of the hippocampal architecture.

The researchers then looked at the effects of the structural abnormalities on function, and found that 2 weeks after the blast exposure the mice were showing impairments in learning and memory tasks, while gross neurologic function, as reflected in movement and exploration activities, remained intact.

These impairments persisted for up to a month, with memory retrieval measures being significantly worse (P<0.05) compared with effects seen in sham-blast control animals, suggesting a long-term loss of plasticity in the neuronal synapses.

Finally, because the experiments suggested that acceleration effects on the head might be responsible for the injury, they immobilized the animals' heads during a blast, and found that memory retention in that group remained normal.

The findings in this study "suggest that [traumatic brain injury] induced by different insults under different conditions can trigger common pathogenic mechanisms leading to similar neuropathology and sequelae," the researchers stated.

In addition, the study "raises concern that blast exposure may increase risk for later development of CTE and associated neurobehavioral sequelae," they warned.

In an editorial accompanying the study, Sam Gandy, MD, PhD, of Mount Sinai School of Medicine in New York City, and Steven T. DeKosky, MD, of the University of Virginia in Charlottesville, noted that an estimated 285,000 veterans of Iraq and Afghanistan have been diagnosed with traumatic brain injury.

Gandy and DeKosky explained that they too have been studying brain injury and CTE among athletes, and noted that carriers of the apolipoprotein E (APOE) ε4 allele, who have an increased risk for Alzheimer's disease, also may be more likely to develop CTE.

However, they argued that it would be premature to initiate widespread testing for the allele in schools or among military recruits at present, because little is known as yet about the life course of CTE and the influence of the allele and other factors.

Rather, they recommended setting up a network of research centers focusing on traumatic brain injury and CTE that would enroll adolescents exposed to sports head injury who have varying apolipoprotein alleles and different ethnicities.

The participants would maintain a lifelong diary of concussive injuries, and if possible, would use "smart helmets" that could measure the various impact forces on the head and brain.

The results could then be analyzed according to apolipoprotein ε4 status to estimate the genetic contribution.

Although the project would be lengthy and expensive, it ultimately might help prevent large numbers of cases of dementia, the editorialists suggested.

"If lifestyle modifications for APOE ε4 carriers -- such as avoiding high-impact sports or opting for military careers that do not put the brain at risk -- can reduce dementia prevalence in 2050 by even 1%, we would gain an annual savings of $10 billion in costs of care -- and immeasurable savings in terms of human suffering," they wrote.

One co-author is an advisory board member of Immunotrex Biologics, while all other authors had no competing interests.

Reviewed by Zalman S. Agus, MD Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner

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